Assessment by 1H NMR spectroscopy of the structural behaviour of human parathyroid-hormone-related protein(1-34) and its close relationship with the N-terminal fragments of human parathyroid hormone in solution.
Human parathyroid-hormone-related protein (hPTHrP) is a hormone that is over-expressed by a large number of tumors and is produced by a variety of normal cells. Its main biological functions are shown by the N-terminal fragment (1-34) and are similar to those of parathyroid hormone with which it shares a common G-protein-coupled receptor. Hence to gain insight into the structure-function relationship of these hormones we have investigated the solution structure of hPTHrP(1-34) in pure water alone and have monitored the effect of adding TFE. CD spectra in pure water showed that it only possesses a small content of alpha-helical secondary structure, which from the NMR data, consists of a short unstable helix between Gln-16 and Leu-24 with the rest of the peptide in an essentially unstructured state. On adding 50% TFE (v/v) there was a considerable increase in stable secondary structure, without any evidence of stable tertiary structure. The subsequent structure calculations showed the presence of two well defined helices, from Ser-3 to Gly-12 and from Asp-17 to Thr-33, connected by a flexible linker. The similarity in behaviour of hPTHrP(1-34) and the N-terminal fragments of PTH under various solution conditions is shown from the 1H NMR data presented here and an extensive review of the literature data.
Gronwald
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Abteilung für Strukturforschung, GBF-Gesellschaft für Biotechnologische Forschung, Braunschweig, Germany.
Schomburg
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D
Tegge
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Wray
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V
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010281:Parathyroid Hormone / Q000737:chemistry*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D011522:Protons; D012996:Solutions
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D011522:Protons; D012996:Solutions; C054296:parathyroid hormone-related protein (1-34)